The two major clinical variants of systemic sclerosis, diffuse scleroderma (DS) and the CREST syndrome, are characterized serologically by the presence of circulating auto antibodies directed against a marker antigen which appears to be specific for each of these variants. The specific antigen for DS is the 105 kd topoisomerase I and for CREST, an 80 kd kinetochore protein. The production of these autoantibodies suggests the hypothesis that they represent a response to an etiological event, possibly viral, bearing identical or similar epitopes. To obtain evidence for or against the molecular mimicry hypothesis of antibody induction in systemic sclerosis, we will characterize the epitopes of these two antigens. The proposed studies aim at demonstrating that these very specific marker autoantibodies represent footprints of the original etiological agent or insult and may therefore yield valuable information regarding the etiology of these incurable autoimmune diseases.